Genetic makeup may affect a person's risk of concussion

Thomas McAllister of the Indiana University School of Medicine reviews data linking genetics and concussion-related brain injury. Such research may answer questions about preventing dementia.Photo by Liz Kaye/IU Communications

By Eric NiilerSpecial To The Washington Post.

Scientists studying head injuries have found something surprising: Genes may make some people more susceptible to concussion and trauma than others.

A person's genetic makeup, in fact, may play a more important role in the extent of injury than the number of blows a person sustains.

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While this research is still in its infancy, these scientists are working toward developing a blood test that may one day help a person decide -- based on his or her genetic predisposition -- whether to try out for the football team, or perhaps take up swimming or chess instead.

"Until now, all the attention has been paid to how hard and how often you get hit," said Thomas McAllister, a professor of clinical psychiatry at the Indiana University School of Medicine."No doubt that's important. But it's also becoming clear that it's probably an interaction between the injury and the genetics of the person being injured."

This research is being spurred by fears that some athletes and many returning soldiers may face a lifetime of problems from head injuries.

The National Football League agreed to settle a class-action concussion lawsuit by retired players last August for $765 million, although a judge rejected the agreement.

In addition, the Pentagon estimates that 294,000 troops, many of whom served in Iraq and Afghanistan, suffered some kind of brain injury since 2000.

"More and more we are noticing our servicemen are coming home with significant problems with brain function," said Daniel Perl, a neuropathologist at the Center for Neuroscience and Regenerative Medicine at the Pentagon's Uniformed Services University for Health Sciences in Bethesda, Md. "We don't know much about the biology of this. We need to get down to cellular level of resolution, how the brain starts to repair itself."

The genes that scientists are looking at may also be related to the development of Alzheimer's disease. These genes encode for the production of proteins that may affect the ability to bounce back from a blow to the head, either from a collision on the playing field or a bomb blast in a war zone.

Some of these genes are key to cleaning up damaged brain cells, while others are important for retention of memory and attention afterward.

Two of the genes involved in recovery after a brain injury may be tau and APOE. Last April, researchers looking at a group of college athletes presented a paper showing a link between the players' reaction time and a particular variation of each of those genes.

The study, which included 3,218 football players and male and female soccer players, did extensive testing on 131 of them.

All people carry the APOE gene, which has many variations. A 2010 study found that athletes carrying three of the gene's four minor variations were 10 times as likely as those who did not to have reported a concussion and more than eight times as likely to have suffered brain injury as a result.

Scientists have known about the dangers of getting hit on the head since the 1920s, when they diagnosed a form of dementia in boxers. They called it dementia pugilistica or "punch-drunk syndrome." In recent years, the same condition has become known as chronic traumatic encephalopathy, or CTE.

Last year, McAllister and his colleagues completed a study comparing college football players with a group of track and field athletes from the same university. They tested both groups for cognition and memory, and they performed sophisticated imaging that measured changes in their brain cells from the beginning of the season to the end.

While the two groups scored equally on the tests, they found that about one in five football players experienced changes to the corpus collossum, a bundle of neural fibers that facilitates communication between the brain's hemispheres. The brains of the track and field athletes did not show such changes.

McAllister said the degree of change was related to how hard and how often the football players had been hit during the season, something measured with small accelerometers implanted in their helmets.

"We don't know if we studied them five or 10 years later if they would be doing all right," McAllister said. "It's possible (the changes) may heal or reverse themselves during the offseason, but we don't know."

The types of athletes discovered to be developing CTE have expanded in recent years to include hockey stars, NASCAR drivers and baseball players. This year, Major League Baseball instituted a rule to reduce collisions between base runners and catchers at home plate.

People with CTE have an abnormal buildup of a protein that can block or disable neural pathways controlling such things as memory, judgment and fear. CTE can be diagnosed only after death and has been linked to psychological problems including depression, anxiety and substance abuse.

But researchers still don't know whether athletes should be worried about big hits that cause concussions, or smaller "pre-concussive" collisions that occur as a routine part of contact sports.

McAllister said that the new genetic research may answer some questions about which genes can make CTE worse or prevent it from developing.

Some researchers caution that it's too early to connect genes and susceptibility to brain trauma. One of them is Vassilis Koliatsos, a neurologist at the Johns Hopkins School of Medicine. He notes that doctors can't diagnose CTE unless they examine the patient's brain after death -- and that makes it hard to figure out how it developed in the first place.

Koliatsos also says that many athletes -- and soldiers -- get hit on the head and recover without developing a degenerative disease such as CTE. But the interplay between genes and behavior is hard to pin down.

People who have a more risk-taking personality, for example, are likely to take part in activities that may expose them to collisions and accidents that lead to concussions.

"You may be a quick gun and have gotten into fights," Koliatsos said. "You may like to drink." It's "not only genes," he says, "but experience."

Koliatsos and others say that until there's a better way to predict who will suffer long-term brain injuries based on their genetic makeup, it may be a good step to prevent more injuries in the meantime by developing a better test for concussions using biomarkers, or bits of protein the brain produces when its injured.

Currently, doctors and athletic trainers check for a player's concussion based on symptoms such as loss of consciousness, confusion and headache. But it can be subjective and inaccurate, making it difficult to determine which players should come out of a game. A more accurate rapid blood test for biomarkers could help coaches and trainers make better decisions more easily.

"Some of this demographic may not be compatible with playing sports, period," Koliatsos said.

Swedish researchers reported in March that they had found elevated levels of total tau, or T-tau, in the blood of hockey players after they had taken blows to the head. Some U.S. biotech firms are working with Pentagon funding to develop such a test for soldiers as well.

Until researchers can better determine the biology and genetics of what happens when our brains get rattled, Koliatsos said there are some simple rules to prevent long-term injuries.

"If you had one concussion, make sure you recover fully before you have another one. Or if you have too many, that you stop altogether. It's common sense."

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